ABSTRACT
The rising burden of antimicrobial resistance and increasing infectious disease outbreaks, including the recent COVID-19 pandemic, has led to a growing demand for the development of natural products as a valuable source of leading medicinal compounds. There is a wide variety of active constituents found in plants, making them an excellent source of antimicrobial agents with therapeutic potential as alternatives or potentiators of antibiotics. The structural diversity of phytochemicals enables them to act through a variety of mechanisms, targeting multiple biochemical pathways, in contrast to traditional antimicrobials. Moreover, the bioactivity of the herbal extracts can be explained by various metabolites working in synergism, where hundreds to thousands of metabolites make up the extract. Although a vast amount of literature is available regarding the use of these herbal extracts against bacterial and viral infections, critical assessments of their quality are lacking. This review aims to explore the efficacy and antimicrobial effects of herbal extracts against clinically relevant gastrointestinal infections including pathogenic Escherichia coli, toxigenic Clostridioides difficile, Campylobacter and Salmonella species. The review will discuss research gaps and propose future approaches to the translational development of plant-derived products for drug discovery purposes for the treatment and prevention of gastrointestinal infectious diseases.
ABSTRACT
The current COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a worldwide health crisis, necessitating coordinated scientific research and urgent identification of new drug targets for treatment of COVID-19 lung disease. The covid19-nmr consortium seeks to support drug development by providing publicly accessible NMR data on the viral RNA elements and proteins. The SARS-CoV-2 genome comprises a single RNA of about 30 kb in length, in which 14 open reading frames (ORFs) have been annotated, and encodes approximately 30 proteins. The first two-thirds of the SARS-CoV-2 genome is made up of two large overlapping open-reading-frames (ORF1a and ORF1b) encoding a replicase polyprotein, which is subsequently cleaved to yield 16 so-called non-structural proteins. The non-structural protein 1 (Nsp1), which is considered to be a major virulence factor, suppresses host immune functions by associating with host ribosomal complexes at the very end of its C-terminus. Furthermore, Nsp1 facilitates initiation of viral RNA translation via an interaction of its N-terminal domain with the 5' untranslated region (UTR) of the viral RNA. Here, we report the near-complete backbone chemical-shift assignments of full-length SARS-CoV-2 Nsp1 (19.8 kDa), which reveal the domain organization, secondary structure and backbone dynamics of Nsp1, and which will be of value to further NMR-based investigations of both the biochemical and physiological functions of Nsp1.